C. Rationale of Proposed Benefit of Research Drug-induced QT prolongation is a significant public health risk and a major barrier to drug development19-21. For example, cisapride, an esophageal motility agent used for gastro-esophageal reflux, may have resulted in more than 80 deaths before it was pulled from the market22. In addition to identification of culprit medications, there are also characteristics of the vulnerable patient, including female sex23, bradycardia24, hypokalemia25, and genetic predisposition by rare mutations3, 6, 26, that place certain individuals at higher risk of fatal arrhythmia. Identification of these at-risk individuals with the use of genetic markers would represent a critical advance toward safer pharmacotherapy7. The basis of this study is to expand the use of genetics beyond rare family mutations that predispose to risk of QT prolongation to large-scale screening of the general population by genotyping (assaying for specific variants) for relatively common polymorphisms that could increase risk of QT prolongation, and subsequent torsade de pointes.